Cribriform tumor of the skin: identification of 6q and 9q loss as a recurrent cytogenomic alteration

Abstract

Cribriform tumor is a rare sweat-gland neoplasm of uncertain malignant potential. Although its histopathologic features are well described, the molecular underpinnings of cribriform tumor remain incompletely characterized. We performed comprehensive molecular profiling of six cribriform tumors from three institutions using whole-exome sequencing, transcriptome sequencing, and SNP-array copy number analysis. The cohort included three women and three men (median age, 54 years; range, 40-66), with tumors measuring 0.3-2.0 cm. Most arose on the extremities, with one located on the back. The most consistent genomic alteration was arm-level losses of chromosomes 6q and 9q, detected in five of six cases. These alterations were validated across independent sequencing and SNP-array platforms. Whole-exome sequencing identified likely pathogenic variants in two tumors (CHEK2 p.R145W and NF1 p.R1830H). No gene fusions were detected. Taken together, these findings provide independent confirmation that 6q/9q loss represents a consistent cytogenomic alteration in cribriform tumor, supporting its utility as a molecular hallmark of this tumor.

Keywords: adnexal neoplasm; copy number alteration; cribriform tumor; next-generation sequencing; sweat gland neoplasm.